This invention relates to methods for permanently joining collagen-containing materials.
Many medical procedures necessitate joining two separate tissue pieces in order to promote wound healing or fusion of the pieces. In addition, many procedures require the connection of a prosthesis to a tissue within the body. These procedures can be done with conventional suturing, stapling, or with newer methods of suture-less tissue repair. However, conventional suturing techniques are time-consuming, and sutures and staples introduce foreign materials into the tissue, thus increasing the risk of infection or adverse immunological reaction. Suturing also disrupts the normal growth and cellular organization of the tissue and increases the risk of scar tissue formation which can interfere with the function of the native tissue, e.g., by partially occluding flow of blood through a sutured vessel. Additionally, scar tissue may create undesired irregularities in the skin. Sutures also leak, which can cause complications, e.g., gastric fluid leakage after gut surgery.
Suture-less joining of tissues has been achieved by "gluing" tissue segments together, using either foreign substances such as cyanomethacrylates, or naturally occurring compounds such as thrombin and fibrin. In addition, suture-less joining or "welding" of tissues has been accomplished with lasers, such as CO.sub.2, Nd:YAG, THC:YAG, argon, and near infra-red diode lasers. For example, welding of connective tissues was described by Jain, J. Microsurg. 1:436-439 (1980) and Dew et al., Lasers Surg. Med. 3:135 (1983), who used low-power lasers, e.g., argon-ion, Nd:YAG, and CO.sub.2 lasers, to permanently attach wellapproximated tissues.
Only connective tissues can be welded, including blood vessel walls, tendon, fascia, some muscle, skin, biliary tissue, epineurium, nerves, urethra, fallopian tube, vas deferens, and gut. Fat and highly cellular tissues do not weld. As a result, it has been suggested that some type of collagen is involved. For example, Schoeber at al., Science, 232:1421-1422 (1986) showed by electron microscopy that denatured collagen was present in the region of argon-ion laser welded tissue. However, Schoeber's study showed gross thermal denaturation extending hundreds of .mu.m on either side of the weld anastomosis. Further, it is known that laser welding results in the formation of collagen-collagen and collagen-elastin bonds (White et al., Lasers Surg. Med., 8:83-89 (1988)).
One use for tissue welding that has been of interest is vascular repair. White et al. (1988), showed that argon-ion laser welded vessels heal with the same strength over time as sutured vessels (after the sutures were removed), but with less foreign body reaction and better mechanical compliance. White et al., J. Vasc. Surg. 6:447-453 (1987), also welded arteriovenous shunts in patients requiring hemodialysis.
In spite of improvements in technique, laser tissue welding is not widely used because it is technically demanding, and the welds are weak. For example, White et al., Lasers Surg. Med., 6:137-141 (1986), reported that the tensile strength of laser-welded arteries was less than that of sutured arteries during the initial weeks following the surgical procedure. Thus, researchers have attempted to strengthen laser welds by applying fibrinogen (Oz et al., J. Vasc. Surg., 11:718-725 (1990)), fibrin (Grubbs et al., J. Surg. Res., 45:112-119 (1988)), or albumin (Poppas et al., J. Urology, 139:415-417 (1988)) to the weld site. In addition, as described, e.g., in Oz et al., (1990), and Decoste et al., Lasers Surg. Med., 12:25-32, (1992), dyes, such as fluorescein isothiocyanate and indocyanine green (IG), have been used to enhance absorption of laser radiation at the site to be welded.